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Kidney Week

Abstract: FR-PO224

Levofloxacin Dosing Recommendations for Home Hemodialysis (HHD)

Session Information

  • Pharmacology
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics‚ -Dynamics‚ -Genomics)

  • 1900 Pharmacology (PharmacoKinetics‚ -Dynamics‚ -Genomics)

Authors

  • Jang, Soo min, Loma Linda University, Loma Linda, California, United States
  • Lewis, Susan J., University of Findlay College of Pharmacy, Findlay, Ohio, United States
  • Mueller, Bruce A., University of Michigan College of Pharmacy, Ann Arbor, Michigan, United States
Background

HHD implementation is challenging due to the lack of drug dosing information for HHD. Recommendations for intermittent HD aren’t applicable to HHD due to differences in dialysis frequency, duration, and dialysate volume from intermittent HD.

Methods

Using Monte Carlo simulation, we modelled 7-day therapy for 10 HHD settings (A: 3-h diurnal HHD 4X/week @ dialysate volumes of 30L, 40L, 50L; B: 3-h diurnal HHD 5X/week @ 20L, 30L; C: 7-h nocturnal HHD 3.5X/week @ 30L, 50L, 60L; D: 7-h nocturnal HHD 5X/week @ 30L, 60L) based on published pharmacokinetic data and internal demographic information from NxStage Medical, Inc. Many oral levofloxacin regimens were simulated to predict the probability of target attainment (PTA). Clinical breakpoints were 0.5mg/L for E. coli, 1mg/L for P. aeruginosa and 2mg/L for S. pneumoniae. The pharmacodynamic (PD) targets were: AUC24h:MIC ≥125 for each 24 h for Gram-negative infections and AUC24h:MIC ≥50 for Gram-positive infections. We have aimed to predict the smallest oral levofloxacin doses that achieved PTA >90% for each HHD setting. Maximum daily dosing for oral levofloxacin approved by the U.S. Food and Drug Administration is 750mg daily, hence maximum dose was limited to 750mg daily.

Results

Our analyses indicates that no oral levofloxacin regimen reaches PTA of >90% on Day 1 for all organisms at all dialysate flows. From Day 2 until Day 7, PTA >98% was achieved for E. coli with 500mg every 24h in all 10 HHD settings at different dialysate volumes. For S. pneumoniae, 750mg every 24h was needed to achieve PD target of >90% whereas, 500mg every 24h achieved PTA of >83% on Day 2 and PTA of >96% from Day 3 until Day 7. For P. aeruginosa, 750mg every 24h was needed to achieve PD target of >90% from Day 3 until Day 7.

Conclusion

One levofloxacin 500 mg tablet every 24h for E. coli and S. pneumoniae, and 750mg every 24h for P. aeruginosa would reach the PD target by day 2. However, clinical caution is warranted since this levofloxacin dosing recommendation is higher than those used for intermittent hemodialysis.

Funding

  • Commercial Support